Monday, February 20, 2012

PKMzeta

Via Kevin Drum, the story of the stuff long term memories are made of.

It seems that the archives of memory must be constantly tended at the molecular level, and the archivist is a molecule called PKMzeta.

What does PKMzeta do? The molecule’s crucial trick is that it increases the density of a particular type of sensor called an AMPA receptor on the outside of a neuron. It’s an ion channel, a gateway to the interior of a cell that, when opened, makes it easier for adjacent cells to excite one another. (While neurons are normally shy strangers, struggling to interact, PKMzeta turns them into intimate friends, happy to exchange all sorts of incidental information.) This process requires constant upkeep—every long-term memory is always on the verge of vanishing. As a result, even a brief interruption of PKMzeta activity can dismantle the function of a steadfast circuit.

If the genetic expression of PKMzeta is amped up—by, say, genetically engineering rats to overproduce the stuff—they become mnemonic freaks, able to convert even the most mundane events into long-term memory. (Their performance on a standard test of recall is nearly double that of normal animals.) Furthermore, once neurons begin producing PKMzeta, the protein tends to linger, marking the neural connection as a memory. “The molecules themselves are always changing, but the high level of PKMzeta stays constant,” Sacktor says. “That’s what makes the endurance of the memory possible.”

For example, in a recent experiment, Sacktor and scientists at the Weizmann Institute of Science trained rats to associate the taste of saccharin with nausea (thanks to an injection of lithium). After just a few trials, the rats began studiously avoiding the artificial sweetener. All it took was a single injection of a PKMzeta inhibitor called zeta-interacting protein, or ZIP, before the rats forgot all about their aversion. The rats went back to guzzling down the stuff.

This molecule and its antagonists have lots of scary potential, but it could also say some important things about eidetic memory and IQ, providing a long sought physical substrate for some of the differences we exhibit in learning and recall.

One obvious question is if this stuff is so good for memory, why don't we just make more of it? No doubt there are good evolutionary reasons, probably rooted in the way it does its job, by potentiating neural interactions. Having your PKMzeta cranked too high might just be a molecularly specific way one could be too smart for one's own good.